Journal
ANALYTICAL CHEMISTRY
Volume 89, Issue 11, Pages 6189-6196Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.7b01125
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Funding
- Dutch Technology Foundation STW (NWO-STW Perspectief program) [P12-04]
- Dutch Biomarker Development Center (BDC)
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Analytical methods based on mass spectrometry (MS) have been successfully applied in biomarker discovery studies, while the role of MS in translating biomarker candidates to clinical diagnostics is less pronounced. MALDImnmunoassays methods that combine immunoaffinity enrichment with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric detection are attractive analytical approaches for large-scale sample analysis by virtue of their ease of operation and high throughput capabilities. Despite this fact, MALDImmunoassays are not widely used in clinical diagnostics, which is mainly due to the limited availability of internal standards that can adequately correct for variability in sample preparation and the MALDI process itself. Here we present a novel MALDImmunoassay for quantification of insulin-like growth factor 1 (IGF1) in human plasma. Reliable IGF1 quantification in the range of 10-1000 ng/mL was achieved by employing N-15-IGF1 as internal standard, which proved to be an essential feature of the IGF1 MALDImmunoassay. The method was validated according to U.S. Food and Drug Administration (FDA) guidelines, which included demonstrating the effectiveness of IGF1/IGF binding protein (IGF1/IGFBP) complex dissociation using sodium dodecyl sulfate (SDS). Furthermore, the MALDImmunoassay compared well with the IDS-iSYS IGF1 immunoassay with high correlation (R-2 = 0.99), although substantially lower levels were reported by the MALDImmunoassay. The method was tested on >1000 samples from a cohort of renal transplant recipients to assess its performance in a clinical setting. On the basis of this study, we identified readouts to monitor the quality of the measurements. Our work shows that MALDI-TOF mass spectrometry is suitable for quantitative biomarker analysis provided that an appropriate internal standard, is used and that readouts are monitored to assess the quality of the measurements.
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